Paroxysmal downbeating nystagmus and proton pump inhibitors
Reviewed by Victor Osei-Lah

This case report highlights the effect of long-term use of proton pump inhibitors on the vestibular system. The authors reported a case of a 70-year-old woman who was admitted with delirium, ataxia, slurred speech and slowness of thought. She had sustained a mild head trauma following a fall. Her family noticed some behavioural changes two days before the fall. Past medical history included stable hypertension on 10 mg lisinopril, gastroesophageal reflux disease on 40 mg esomeprazole, dyslipidaemia on atorvastatin 20 mg and osteoporosis. On clinical examination, she was alert but confused, incoherent with normal vital signs. She was unsteady, no limb weakness, saccadic smooth pursuit but no other ocular motor abnormalities. Tendon reflexes were weak but symmetrical. Differential diagnoses considered at this point included post-traumatic confusion, post-ictal confusion, infectious or auto-immune encephalitis, metabolic or toxic encephalopathy and possibly transient global amnesia. Extensive investigations initially revealed hypokalaemia, for which she received treatment. Due to a suspected Wernicke encephalopathy, she was started on vitamin B1. MRI brain on days one and three was essentially normal apart from mild atrophy. EEG was also normal. The patient became more aggressive and agitated from day two on admission. On day five, she had the first attack of severe agitation, arterial hypertension > 180/80 mmHg, tachypnoea > 30/min, tachycardia > 110 bpm, dysarthria and marked spontaneous downbeat nystagmus (DBN), all lasting about one minute. She had repeated vomiting and developed severe ataxia that left her unable to walk unaided or to eat or drink independently. After an attack, she reported visual hallucinations involving people and animals trying to harm her. The attacks occurred five to 10 times a day for three days until hypomagnesemia was diagnosed and treatment commenced for two months. At this stage she was admitted to intensive care for close monitoring. Infection screen and antibody analyses were negative. The paroxysmal attacks consisting of downbeat nystagmus, dysarthria, severe agitation, vomiting, visual hallucinations, hypertensive peaks, tachypnoea and tachycardia reduced after 12 hours of the commencement of magnesium supplementation and progressively disappeared over 48 hours, but full recovery took six weeks. There were two impressive videos showing the DBN before and after treatment. At follow-up it became apparent that the dose of calcium for osteoporosis had been increased 10 days prior to presentation. The eventual diagnosis was hypomagnesemia-induced cerebellar syndrome secondary to prolonged intake of PPI. The high dose of calcium decompensated the hypomagnesemia. Not only do PPIs deplete magnesium in the gut, they can also cause hypocalcaemia and deplete B12 levels. The authors discussed the effect of magnesium metabolism on NMDA receptors in the cerebellum (vermis and nodulus) and the reports that vertical nystagmus, usually paroxysmal and downbeat, has been described to be a typical and specific manifestation of magnesium depletion. This case report is noteworthy and highlights the importance of considering long-term use of PPIs as a potential cause of ataxia, no matter how mild. It also highlights the effectiveness of treating the hypomagnesemia while controlling for the underlying factors.

Paroxysmal downbeat nystagmus, a case report and a review of the literature.
Rhaddioui M, Bisdorff A.
J VESTIB RES
2025;35(6):328–35.